Case report: Clinical, imaging, and genetic characteristics of type B niemann pick disease combined with segawa syndrome diagnosed via dual gene sequencing.

Niemann Pick disease B (NPB) often presents with hepatosplenomegaly and lung pathological changes, but it usually does not present with central nervous system symptoms. This report presents the unique case of a 21-year-old woman with a 10-year history of hard skin and hepatosplenomegaly. Genetic sequencing revealed NPB and also suggested Segawa syndrome. Although symptomatic supportive treatments were administered in an attempt to improve muscle tone and treat the skin sclerosis, their efficacy was not satisfactory, and the patient refused further treatment. This case provides several noteworthy findings. First, although NPB and Segawa syndrome are rare, both are autosomal recessive inherited diseases that share common clinical symptoms and imaging manifestations. Second, when NPB and Segawa syndrome are highly suspected, screening for tyrosine hydroxylase (TH) and sphingomyelin phosphodiesterase-1 (SMPD1) gene mutations is critical to determine an accurate diagnosis. Finally, early diagnosis and comprehensive therapies are crucial for improving the prognosis of patients with NPB and Segawa syndrome.

Nomogram model for predicting cancer-specific mortality in patients with early-onset colorectal cancer: a competing risk analysis insight from the SEER database and an external validation cohort.

Background: Early-onset colorectal cancer (EOCRC) is increasing in incidence and poses a growing threat. Urgent research is needed, especially in survival analysis, to enhance comprehension and treatment strategies. This study aimed to explore the risk factors associated with cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients with EOCRC. Additionally, the study aimed to develop a nomogram predicting CSM using a competitive risk model and validate its accuracy through the use of training, using internal and external cohorts. Methods: Data from EOCRC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database (2008-2017). EOCRC patients who were treated at a tertiary hospital in northeast China between 2014 and 2020 were also included in the study. The SEER data were divided into the training and validation sets at a 7:3 ratio. A univariate Cox regression model was employed to identify prognostic factors. Subsequently, multivariate Cox regression models were applied to ascertain the presence of independent risk factors. A nomogram was generated to visualize the results, which were evaluated using the concordance index (C-index), area under the curve (AUC), and calibration curves. The clinical utility was assessed via decision curve analysis (DCA). Results: Multivariable Cox regression analysis demonstrated that factors such as race, tumor differentiation, levels of carcinoembryonic antigen (CEA), marital status, histological type, American Joint Committee on Cancer (AJCC) stage, and surgical status were independent risk factors for CSM in EOCRC patients. In addition, age, gender, chemotherapy details, CEA levels, marital status, and AJCC stage were established as independent risk factors for OCM in individuals diagnosed with EOCRC. A nomogram was developed using the identified independent risk factors, demonstrating excellent performance with a C-index of 0.806, 0.801, and 0.810 for the training, internal validation, and external validation cohorts, respectively. The calibration curves and AUC further confirmed the accuracy and discriminative ability of the nomogram. Furthermore, the DCA results indicated that the model had good clinical value. Conclusions: In this study, a competing risk model for CSM was developed in EOCRC patients. The model demonstrates a high level of predictive accuracy, providing valuable insights into the treatment decision-making process.

Influence of different factors on coseismic deformation of the 2015 Mw7.8 earthquake in Nepal.

In Geophysics, topographic factors are observations that can be directly measured, but they are often ignored to simplify the model. Studying the coseismic deformation caused by earthquakes helps accurately determine the epicenter's parameterization. It provides a reference for the reasonable layout of coseismic observation stations and GNSS observation stations. After the Mw7.8 earthquake in Nepal in 2015, GCMT, USGS, GFZ, CPPT, and other institutions released their epicenter parameter. However, according to their parameters, the coseismic displacements simulated by the spectral-element method are quite different from the GNSS observations. Firstly, this paper inverts the geometric parameters of the seismogenic fault with Nepal's coseismic GNSS displacement. The spectral-element method determines the source's location and depth under the heterogeneous terrain and outputs the source parameters. Among the results of many studies, the surface source is more consistent with the generation mechanism of large earthquakes. Secondly, this paper calculates the fault slip distribution of this earthquake using SDM (Steepest Descent Method) based on GNSS and InSAR data, which is divided into 1500 subfaults, and the moment tensor of each subfault is calculated. This paper investigates the distribution characteristics of the coseismic deformation field of the 2015 Mw 7.8 earthquake in Nepal under three different models. The results show that the influence of topographic factors is ~ 20%, and the influence of heterogeneous factors is ~ 10%. This paper concludes that the influence of topographic factors is much more significant than that of heterogeneous factors, and the influence of both should be addressed in coseismic deformation calculations.

The Variation in Chemical Composition and Source Apportionment of PM2.5 before, during, and after COVID-19 Restrictions in Zhengzhou, China.

Despite significant improvements in air quality during and after COVID-19 restrictions, haze continued to occur in Zhengzhou afterwards. This paper compares ionic compositions and sources of PM2.5 before (2019), during (2020), and after (2021) the restrictions to explore the reasons for the haze. The average concentration of PM2.5 decreased by 28.5% in 2020 and 27.9% in 2021, respectively, from 102.49 µg m-3 in 2019. The concentration of secondary inorganic aerosols (SIAs) was 51.87 µg m-3 in 2019, which decreased by 3.1% in 2020 and 12.8% in 2021. In contrast, the contributions of SIAs to PM2.5 increased from 50.61% (2019) to 68.6% (2020) and 61.2% (2021). SIAs contributed significantly to PM2.5 levels in 2020-2021. Despite a 22~62% decline in NOx levels in 2020-2021, the increased O3 caused a similar NO3- concentration (20.69~23.00 µg m-3) in 2020-2021 to that (22.93 µg m-3) in 2019, hindering PM2.5 reduction in Zhengzhou. Six PM2.5 sources, including secondary inorganic aerosols, industrial emissions, coal combustion, biomass burning, soil dust, and traffic emissions, were identified by the positive matrix factorization model in 2019-2021. Compared to 2019, the reduction in PM2.5 from the secondary aerosol source in 2020 and 2021 was small, and the contribution of secondary aerosol to PM2.5 increased by 13.32% in 2020 and 12.94% in 2021. In comparison, the primary emissions, including biomass burning, traffic, and dust, were reduced by 29.71% in 2020 and 27.7% in 2021. The results indicated that the secondary production did not significantly contribute to the PM2.5 decrease during and after the COVID-19 restrictions. Therefore, it is essential to understand the formation of secondary aerosols under high O3 and low precursor gases to mitigate air pollution in the future.

Pulmonary Edema After Intracranial Aneurysm Clipping in Kyphosis: A Case Report.

Introduction: A 56-year-old female patient was admitted to the hospital for "10+days of right eye droop and 1 day of aggravation". After admission, the physical examination found that the patient had severe scoliosis. 3D reconstruction and enhanced CT scan of the head vessels showed that the right internal carotid artery C6 aneurysms were clipped under general anesthesia. After the operation, the patient had increased airway pressure, with a large number of pink foam sputum attracted from the trachea catheter, and the lungs were scattered with moist rales during auscultation, After the treatment of anti-heart failure, the patient returned to the ICU through the trachea catheter. Eight hours later, the trachea catheter was pulled out and the patient was released from the ventilator. The symptoms were relieved on the fifth day after the operation. This case report describes the perioperative management of intracranial aneurysm with severe scoliosis. After strict monitoring and timely treatment during the perioperative period, the patient turned from crisis to safety, providing some reference for colleagues who encounter such patients in the future. Conclusion: In patients with scoliosis, due to long-term compression of the thorax, pulmonary restrictive ventilation dysfunction, small airway function and diffusion function are reduced, and cardiac function is decreased. Therefore, during the operation of intracranial aneurysms, fluid infusion should be careful, and volume monitoring should be done at all times to maintain the effective circulating blood volume of the body and prevent the aggravation of cardiac insufficiency and pulmonary edema.

Oral Delivery of Anti-Parasitic Agent-Loaded PLGA Nanoparticles: Enhanced Liver Targeting and Improved Therapeutic Effect on Hepatic Alveolar Echinococcosis.

Background: Alveolar echinococcosis (AE) is a lethal parasitic disease caused by infection with the metacestode of the dog/fox tapeworm Echinococcus multilocularis, which primarily affects the liver. Although continued efforts have been made to find new drugs against this orphan and neglected disease, the current treatment options remain limited, with drug delivery considered a likely barrier for successful treatment. Methods: Nanoparticles (NPs) have gained much attention in the field of drug delivery due to their potential to improve delivery efficiency and targetability. In this study, biocompatible PLGA nanoparticles encapsulating a novel carbazole aminoalcohol anti-AE agent (H1402) were prepared to promote the delivery of the parent drug to liver tissue for treating hepatic AE. Results: H1402-loaded nanoparticles (H1402-NPs) had a uniform spherical shape and a mean particle size of 55 nm. Compound H1402 was efficiently encapsulated into PLGA NPs with a maximal encapsulation efficiency of 82.1% and drug loading content of 8.2%. An in vitro uptake assay demonstrated that H1402-NPs rapidly penetrated the in vitro cultured pre-cyst wall and extensively accumulated in the pre-cysts of E. multilocularis within only 1 h. The biodistribution profile of H1402-NPs determined through ex vivo fluorescence imaging revealed significantly enhanced liver distribution compared to unencapsulated H1402, which translated to improved therapeutic efficacy and reduced systemic toxicity (especially hepatotoxicity and cytotoxicity) in a hepatic AE murine model. Following a 30-day oral regimen (100 mg/kg/day), H1402-NPs significantly reduced the parasitic burden in both the parasite mass (liver and metacestode total weight, 8.8%) and average metacestode size (89.9%) compared to unmedicated infected mice (both p-values < 0.05); the treatment outcome was more effective than those of albendazole- and free H1402-treated individuals. Conclusion: Our findings demonstrate the advantages of encapsulating H1402 into PLGA nanoparticles and highlight the potential of H1402-NPs as a promising liver-targeting therapeutic strategy for hepatic AE.

Phase Separation in cGAS-STING Signaling: Cytosolic DNA Sensing and Regulatory Functions.

Phase separation is a crucial biophysical process that governs cellular signaling and function. This process allows biomolecules to separate and form membraneless compartments in response to both extra- and intra-cellular stimuli. Recently, the identification of phase separation in different immune signaling pathways, including the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, has shed light on its tight association with pathological processes such as viral infections, cancers, and inflammatory diseases. In this review, we present the phase separation in cGAS-STING signaling, along with its related cellular regulatory functions. Furthermore, we discuss the introduction of therapeutics targeting cGAS-STING signaling, which plays a pivotal role in cancer progression.

Tetraspanin 4 stabilizes membrane swellings and facilitates their maturation into migrasomes.

Migrasomes are newly discovered cell organelles forming by local swelling of retraction fibers. The migrasome formation critically depends on tetraspanin proteins present in the retraction fiber membranes and is modulated by the membrane tension and bending rigidity. It remained unknown how and in which time sequence these factors are involved in migrasome nucleation, growth, and stabilization, and what are the possible intermediate stages of migrasome biogenesis. Here using live cell imaging and a biomimetic system for migrasomes and retraction fibers, we reveal that migrasome formation is a two-stage process. At the first stage, which in biomimetic system is mediated by membrane tension, local swellings largely devoid of tetraspanin 4 form on the retraction fibers. At the second stage, tetraspanin 4 molecules migrate toward and onto these swellings, which grow up to several microns in size and transform into migrasomes. This tetraspanin 4 recruitment to the swellings is essential for migrasome growth and stabilization. Based on these findings we propose that the major role of tetraspanin proteins is in stabilizing the migrasome structure, while the migrasome nucleation and initial growth stages can be driven by membrane mechanical stresses.

A novel fluorescent molecule based on 1,2,3-triazole for determination of palladium (II) and hydrazine hydrate in aqueous system.

In recent years, hydrazine hydrate has been widely used in various fields as fuel and chemical raw materials, etc. However, hydrazine hydrate is also a potential threat to living body and natural environment. The effective method is urgently needed to detect hydrazine hydrate in our living environment. Secondly, as a precious metal, palladium has attracted more and more attention because of its excellent properties in industrial manufacturing and chemical catalysis. However, its potential danger is also slowly approaching, so it is necessary to find an excellent way to detect palladium, too. Herein, a fluorescent molecule, 4,4',4'',4'''-(1,4-phenylenebis(2H-1,2,3-triazole-2,4,5-triyl)) tetrabenzoic acid (NAT), was synthesized. Firstly, NAT has very high selectivity and sensitivity for determination of Pd2+, because Pd2+ can coordinate well with carboxyl oxygen of NAT. The detection performance of Pd2+ is that the linear range is from 0.06 to 4.50 µM and the detection limit is 16.4 nM. Furthermore, the chelate (NAT-Pd2+) can continue to be used for quantitative determination of hydrazine hydrate with a linear range of 0.05-6.00 µM and the detection limit is 19.1 nM. The interaction time of NAT-Pd2+ and hydrazine hydrate is about 10 min. Of course, it also has good selectivity and strong anti-interference ability for many common metal ions, anions and amine like compounds. At last, the ability of NAT to quantitatively detect Pd2+ and hydrazine hydrate in actual samples has also been verified and the results are very satisfactory.

Nomogram for predicting prolonged postoperative ileus in colorectal cancer based on age and inflammatory markers.

Aim: To explore the relationship between inflammatory markers and prolonged postoperative ileus (PPOI), and to establish a nomogram for predicting PPOI. Patients & methods: The data of 229 patients were analyzed retrospectively. Univariate and multivariate logistic regression analysis were used to analyze the risk factors affecting the occurrence of PPOI. The predictive model of PPOI was established and verified internally. Results: Postoperative PPOI occurred in 87 (38.0%) of all 229 patients. Our study showed that age, preoperative neutrophil-lymphocyte ratio and changes in neutrophil-lymphocyte ratio were independent risk factors for PPOI. Conclusion: The nomograms established based on these independent risk factors have good predictive efficacy and may be able to guide clinicians to individualize the diagnosis and treatment.

[Effect and mechanism of microRNA-155 in chronic obstructive pulmonary disease by targeting PIK3R1].

This study aimed to investigate the effect of microRNA-155 (miR-155) in chronic obstructive pulmonary disease (COPD) and cigarette smoke extract (CSE)-treated airway smooth muscle cells (ASMCs) by targeting phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) to regulate the PTEN/PI3K/Akt signaling pathway. The COPD mouse model was induced by lipopolysaccharide (LPS) combined with passive smoking. After modeling, miR-155 mimics and miR-155 inhibitor were used for intervention treatment. The pulmonary function of each group was detected by an EMKA detector. Hematoxylin-eosin (HE) staining was used to observe the pathological changes and scores of lung tissues. The expression of TNF-α, IL-6, and IL-1ß in bronchial alveolar lavage fluid (BALF) was detected by ELISA. Primary ASMCs were isolated and cultured in adherent tissue culture. The proliferation activity was detected by CCK-8 and EdU assays. Transwell and wound healing assays were used to measure the migration of ASMCs. The targeting relationship between miR-155 and PIK3R1 was validated by a double luciferase reporter gene assay. The expression levels of miR-155 and PIK3R1 mRNA in lung tissues of mice in each group were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was used to detect the expression levels of Ki67, PNCA, PTEN, p-PI3K, PI3K, p85α, p-Akt, and Akt in lung tissues and ASMCs. The results showed that lung function was significantly reduced in the miR-155 mimic group, and the levels of PIK3R1 were significantly increased; while lung function in the miR-155 inhibitor group was significantly improved. The results of HE staining showed that there was obvious inflammatory cell infiltration in the miR-155 mimics group compared to that of the model group. Lung histopathological injury was significantly reduced in the miR-155 inhibitor group, accompanied by decreased expression of Ki67, PNCA, PI3K, p-Akt, increased PTEN and p85α protein levels, and reduced levels of TNF-α, IL-6, and IL-1ß in BALF. The results of the double luciferase reporter gene assay showed that miRNA-155 could target bind to PIK3R1. Compared with those in the CSE+miR-155 NC group, the proliferation and migration of ASMCs were significantly increased in the CSE+miR-155 group. The proliferation and migration of ASMCs were significantly attenuated in the CSE+miR-155+pcDNA PIK3R1 group compared with those in the CSE+miR-155 group, accompanied by decreased expression of Ki67, PNCA, p-Akt and increased PTEN and p85α protein levels. These results suggest that miR-155 activates the PTEN/PI3K/Akt signaling pathway by targeting PIK3R1 to promote the occurrence and development of COPD, which provides new evidence for the use of miR-155 in the treatment of COPD.

The Biosafety Evaluation for Crustaceans: A Novel Molluscicide PBQ Using against Oncomelania hupensis, the Intermediate Host of Schistosoma japonica.

A new formulation (suspension concentrate, SC) of PBQ [1-(4-chlorophenyl)-3-(pyridin-3-yl) urea] was used in water network schistosomiasis-endemic areas to test its molluscicidal efficacy and the acute toxicity to crustaceans. PBQ (20% SC), 26% metaldehyde, and niclosamide suspension concentrate [MNSC (26% SC)] were used both in ditch and field experiments for the molluscicidal efficacy comparison. Acute toxicity tests of two molluscicides were conducted using Neocaridina denticulate and Eriocheir sinensis. Both in the field and ditch experiments, PBQ exhibited comparable molluscicidal efficacy with MNSC. At doses of 0.50 g/m3 and 0.50 g/m2, the snail mortalities were more than 90% three days after PBQ (20% SC) application. Compared with previous tests, PBQ (20% SC) exhibited higher molluscicidal activity than PBQ (25% wettable powder, 25% WP) used in Jiangling and showed similar mollucicidal activity to PBQ (25% WP) used in Dali and Poyang Lake. The 96 h LC50 value of MNSC against Eriocheir sinensis was 283.84 mg a.i./L. At the concentration of PBQ (20% SC) 1000 mg a.i./L, all Eriocheir sinensis were alive. The 96 h LC50 values of PBQ and MNSC against Neocaridina denticulate were 17.67 and 14.05 mg a.i./L, respectively. In conclusion, PBQ (20% SC) had a comparable molluscicidal efficacy with MNSC (26% SC) and PBQ (25% WP). Furthermore, it showed lower toxicity to the crustacean species, better solubility, no floating dust, and convenience for carriage. PBQ (20% SC) was suitable for controlling snails in the water network schistosomiasis-endemic areas.

Haze caused by NOx oxidation under restricted residential and industrial activities in a mega city in the south of North China Plain.

The formation of secondary aerosol species, including nitrate and sulfate, induces severe haze in the North China Plain. However, despite substantial reductions in anthropogenic pollutants due to severe restriction of residential and industrial activities in 2020 to stop the spread of COVID-19, haze still formed in Zhengzhou. We compared ionic compositions of PM2.5 during the period of the restriction with that immediately before the restriction and in the comparison period in 2019 to investigate the processes that caused the haze. The average concentration of PM2.5 was 83.9 µg m-3 in the restriction period, 241.8 µg m-3 before the restriction, and 94.0 µg m-3 in 2019. Nitrate was the largest contributor to the PM2.5 in all periods, with an average mass fraction of 24%-30%. The average molar concentration of total nitrogen compounds (NOx + nitrate) was 0.89 µmol m-3 in the restriction period, which was much lower than that in the non-restriction periods (1.85-2.74 µmol m-3). In contrast, the concentration of sulfur compounds (SO2 + sulfate) was 0.34-0.39 µmol m-3 in all periods. The conversion rate of NOx to nitrate (NOR) was 0.35 in the restriction period, significantly higher than that before the restriction (0.26) and in 2019 (0.25). NOR was higher with relative humidity in 40-80% in the restriction period than in the other two periods, whereas the conversion rate of SO2 to sulfate did not, indicating nitrate formation was more efficient during the restriction. When O3 occupied more than half of the oxidants (Ox = O3 + NO2), NOR increased rapidly with the ratio of O3 to Ox and was much higher in the daytime than nighttime. Therefore, haze in the restriction period was caused by increased NOx-to-nitrate conversion driven by photochemical reactions.

Haze Occurrence Caused by High Gas-to-Particle Conversion in Moisture Air under Low Pollutant Emission in a Megacity of China.

Haze occurred in Zhengzhou, a megacity in the northern China, with the PM2.5 as high as 254 µg m-3 on 25 December 2019, despite the emergency response measure of restriction on the emission of anthropogenic pollutants which was implemented on December 19 for suppressing local air pollution. Air pollutant concentrations, chemical compositions, and the origins of particulate matter with aerodynamic diameter smaller than 2.5 µm (PM2.5) between 5-26 December were investigated to explore the reasons for the haze occurrence. Results show that the haze was caused by efficient SO2-to-suflate and NOx-to-nitrate conversions under high relative humidity (RH) condition. In comparison with the period before the restriction (5-18 December) when the PM2.5 was low, the concentration of PM2.5 during the haze (19-26 December) was 173 µg m-3 on average with 51% contributed by sulfate (31 µg m-3) and nitrate (57 µg m-3). The conversions of SO2-to-sulfate and NOx-to-nitrate efficiently produced sulfate and nitrate although the concentration of the two precursor gases SO2 and NOx was low. The high RH, which was more than 70% and the consequence of artificial water-vapor spreading in the urban air for reducing air pollutants, was the key factor causing the conversion rates to be enlarged in the constriction period. In addition, the last 48 h movement of the air parcels on 19-26 December was stagnant, and the air mass was from surrounding areas within 200 km, indicating weather conditions favoring the accumulation of locally-originated pollutants. Although emergency response measures were implemented, high gas-to-particle conversions in stagnant and moisture circumstances can still cause severe haze in urban air. Since the artificial water-vapor spreading in the urban air was one of the reasons for the high RH, it is likely that the spreading had unexpected side effects in some certain circumstances and needs to be taken into consideration in future studies.

Polyvinylamine with moderate binding affinity as a highly effective vehicle for RNA delivery.

Polymeric carriers for RNA therapy offer potential advantages in terms of low immunogenicity, promoting modifiability and accelerating intracellular transport. However, balancing high transfection efficacy with low toxicity remains challenging with polymer-based vehicles; indeed, polyethyleneimine (PEI) remains the "gold standard" polymer for this purpose despite its significant toxicity limitations. Herein, we demonstrate the potential of polyvinylamine (PVAm), a commodity high-charge cationic polymer used in the papermaking industry and has similar structure with PEI, as an alternative carrier for RNA delivery. High levels of transfection of normal, tumor, and stem cells with a variety of RNA cargoes including small interfering RNA (siRNA), microRNA (miRNA), and recombinant RNA can be achieved in vitro under the proper complex conditions. While, both the anti-tumor effect achieved in a xenograft osteosarcoma model and lipid-lowering activity observed in a hyperlipidemia mice indicate the potential for highly effective in vivo activity. Of note, both the transfection efficiency and the cytotoxicity of PVAm compare more favorably with those of PEI, with PVAm offering the additional advantages of simpler purification and significantly lower cost. In addition, the mechanism for the difference in transfection efficiency between PVAm and PEI is explored by molecular docking as well as analyzing the process of association and dissociation between polymers (PVAm and PEI) and nucleic acids. Our research provides a novel, non-toxic, and cost-effective carrier candidate for next generation RNA therapy, and elucidates the potential mechanism of PVAm for its efficient delivery of RNA.

Puerarin inhibits FUNDC1-mediated mitochondrial autophagy and CSE-induced apoptosis of human bronchial epithelial cells by activating the PI3K/AKT/mTOR signaling pathway.

Increasing evidence suggests that the pathogenesis of chronic obstructive pulmonary disease (COPD) is associated with FUN14 domain protein 1 (FUNDC1)-mediated mitophagy. Recently, studies have reported that puerarin has protective effects against excessive oxidative damage in cells. Therefore, we hypothesized that puerarin may be involved in COPD progression via regulating FUNDC1 mediated mitophagy. We found that the viability of cigarette smoke extract (CSE)-stimulated human bronchial epithelial cells (HBECs) was enhanced and apoptosis was reduced after treatment with different concentrations of puerarin. Puerarin reversed mitochondrial membrane potential (MMP) levels and ATP content, and decreased reactive oxygen species (ROS) content in CSE stimulated HBECs. Moreover, puerarin significantly inhibited apoptosis related proteins, as well as the expression of mitophagy related proteins. After inhibition of FUNDC1 phosphorylation by protein phosphatase inhibitor (PH0321), puerarin restored MMP level, decreased ROS content, promoted ATP synthesis, and downregulated autophagy related protein expression in HBECs. In addition, mitochondrial division inhibitor (Mdivi) inhibited the expression of autophagy related proteins and reduced apoptosis after blocking cell autophagy, which was the same as the inhibition of puerarin. Finally, puerarin activated the PI3K/Akt/mTOR signaling pathway to participate in COPD progression by up regulating the phosphorylation levels of PI3K, Akt and mTOR.

Bergamottin promotes osteoblast differentiation and bone formation via activating the Wnt/ß-catenin signaling pathway.

Osteoporosis is one of the most common bone disorders that seriously affect the health and life quality of elderly individuals. Reduced osteoblast differentiation and bone formation lead to changes in bone volume and microarchitecture, leaving the bones vulnerable to fracture. Bergamottin (BM) is a natural compound derived from various citrus fruits and possesses multiple biological activities including anti-adipogenesis function. This study aimed to evaluate the effects of BM on osteoblast differentiation and its potential anti-osteoporosis capacity, as well as to explore the underlying mechanism. We demonstrated that BM, as a positive regulator for osteogenesis, significantly promoted osteoblast differentiation and bone formation. Mechanically, BM activated the Wnt/ß-catenin signaling pathway and promoted the nuclear translocation of ß-catenin. In addition, BM dramatically upregulated the expression of ß-catenin, enhanced the transcriptional activation of T cell factor 7 (TCF7), and increased the expression of Runt-related transcription factor 2 (Runx2). Taken together, this study revealed that BM enhanced osteoblast differentiation and attenuated ovariectomy (OVX)-induced bone loss, possessing the potential to be developed into a food ingredient or supplement for preventing osteoporosis.

Control of the Invasive Agricultural Pest Pomacea canaliculata with a Novel Molluscicide: Efficacy and Safety to Nontarget Species.

The golden apple snail Pomacea canaliculata is an invasive pest that causes extensive damage to agricultural production. P. canaliculata is also an intermediate host of Angiostrongylus cantonensis, which causes human eosinophilic meningitis. In this study, the molluscicidal activity and safety profile of a novel molluscicide PBQ [1-(4-chlorophenyl)-3-(pyridin-3-yl)urea] were evaluated. PBQ exhibited strong molluscicidal potency against adult and juvenile snails (LC50 values of 0.39 and 0.07 mg/L, respectively). In field trials, PBQ killed 99.42% of the snails at 0.25 g a.i./m2. An acute toxicity test in rats demonstrated that PBQ is a generally nonhazardous chemical. PBQ is also generally safe for nontarget organisms including Brachydanio rerio, Daphnia magna, and Apis mellifera L. Transcriptomics analysis revealed that PBQ had a significant impact on the carbohydrate and lipid metabolism pathways, which provided insights into its molluscicidal mechanism. These results suggest that PBQ could be developed as an effective and safe molluscicide for P. canaliculata control.

Comparative proteomics suggests the mode of action of a novel molluscicide against the invasive apple snail Pomacea canaliculata, intermediate host of Angiostrongylus cantonensis.

Angiostrongylus cantonensis is a zoonotic parasitic nematode that is the most common cause of human eosinophilic meningitis. The invasive apple snail Pomacea canaliculata is an important intermediate host of A. cantonensis and contributes to its spread. P. canaliculata control will help prevent its invasion and transmission of A. cantonensis. The new molluscicide PBQ (1-(4-chlorophenyl)-3-(pyridin-3-yl)urea) exhibits great potency against P. canaliculata and has low toxicity against mammals and non-target aquatic organisms. We studied the mode of action of PBQ using TMT-based comparative quantitative proteomics analysis between PBQ-treated and control P. canaliculata snails. A total of 3151 proteins were identified, and 245 of these proteins were significantly differentially expressed with 135 downregulated and 110 upregulated. GO and KEGG enrichment analyses identified GO terms and KEGG pathways involved in de novo purine biosynthesis, ribosome components and translation process were significantly enriched and downregulated. The results indicated that PBQ treatment had substantial effects on the synthesis of genetic material, translation process, and protein synthesis of P. canaliculata and were likely the main cause of snail mortality.

Crystal Structure of Inorganic Pyrophosphatase From Schistosoma japonicum Reveals the Mechanism of Chemicals and Substrate Inhibition.

Soluble inorganic pyrophosphatases (PPases) are essential for facilitating the growth and development of organisms, making them attractive functional proteins. To provide insight into the molecular basis of PPases in Schistosoma japonicum (SjPPase), we expressed the recombinant SjPPase, analyzed the hydrolysis mechanism of inorganic pyrophosphate (PPi), and measured its activity. Moreover, we solved the crystal structure of SjPPase in complex with orthophosphate (Pi) and performed PPi and methylene diphosphonic acid (MDP) docking into the active site. Our results suggest that the SjPPase possesses PPi hydrolysis activity, and the activity declines with increased MDP or NaF concentration. However, the enzyme shows unexpected substrate inhibition properties. Through PPi metabolic pathway analysis, the physiological action of substrate inhibition might be energy saving, adaptably cytoprotective, and biosynthetic rate regulating. Furthermore, the structure of apo-SjPPase and SjPPase with Pi has been solved at 2.6 and 2.3 Å, respectively. The docking of PPi into the active site of the SjPPase-Pi complex revealed that substrate inhibition might result from blocking Pi exit due to excess PPi in the SjPPase-Pi complex of the catalytic cycle. Our results revealed the structural features of apo-SjPPase and the SjPPase-Pi complex by X-ray crystallography, providing novel insights into the physiological functions of PPase in S. japonicum without the PPi transporter and the mechanism of its substrate inhibition.